The present invention relates to mass spectrometry apparatus and methods for obtaining information of molecular weight and structural composition of compounds, such as has been previously obtained by mass spectrometers generally and more specifically by tandem mass spectrometers. The invention can also be used as a detector in conventional mass spectrometers to further mass resolve detected ions.
In simple mass spectrometers, ions are produced from solids, liquids, or gases by some ionizing event such as electron beam bombardment of a gas. The ions are detected after mass separation by various techniques such as magnetic analyzers, quadrupole or monopole r-f field mass filters, time-of-flight separators, Fourier transform mass separators, etc. The detected ions can be elemental or molecular ions characteristic of the specimen, fragment ion products caused by the ionizing event, or fragment ions due to decomposition of a precursor ion which are produced either in the ion source or along the ion path to the detector.
More recently, mass spectrometers have been placed in tandem in which the first spectrometer mass separates an ion species which is caused to fragment or dissociate, such as by metastable decomposition, collision induced dissociation (CID) or collisionally activated dissociation (CAD), into lower mass product particles (daughters) of which some are ionic and some are neutral. The ion daughters are subsequently mass separated to give a daughter ion spectrum of the products of fragmentation originating from precursor ion species. This tandem construction is known as MS/MS. Such a combination of mass spectrometers allows analysis of specific daughter ions which are unique to a specific precursor ion in the presence of mixtures or with complex, high mass compounds for which simple mass spectrometric separation would allow contributions to the ion signal from other interfering ions or fragments thus causing great difficulty and confusion for interpretation. MS/MS thus greatly increases the information gathering capability of simple mass spectrometers.
Although MS/MS has many benefits and uses, inherent disadvantages exist. For example, such devices make inefficient use of the produced ions in that many of the ions are destroyed due to system losses rather than being detected. Additionally, all ion particles which are not selected by the first mass analyzer are discarded thus causing loss of data as well as hindering unique ion characterization as will become apparent in this invention. Other disadvantages include difficulty in quantifying the ensuing data, since the numbers of each type of fragmentation event is not known exactly, and destructive losses to the specimen due to the requirement for relatively large ion currents.
Another form of mass spectrometry is known as time-of-flight mass spectromety. In a time-of-flight mass spectrometer ions are produced and then accelerated, either in a constant-energy or a constant-momentum mode. In either case, lighter (lower mass) ions are accelerated to higher velocities than the heavier ions. The ions then enter a drift region or flight tube which establishes an ion path length, and which is followed by an ion detector. In the drift region, the ions separate along the ion path as a function of their velocity and thus arrive at the detector at different times depending upon their velocities, and therefore, depending upon their mass.
To permit measurement of flight time, ions in a time-of-flight mass spectrometer are bunched, typically by means of a pulsed source, and all ions of a given bunch enter the drift region at substantially the same position and time. By correlating ion pulsing or bunching with arrival time of various ions at the detector, the time-of-flight of each individual ion or group of identical-mass ions can be determined. Ion velocity follows from the simple relationship: EQU (Velocity)=(Path Length)/(Time-Of-Flight).
From velocity, ion mass can be calculated, taking into account the characteristics of the ion accelerator.
A fundamental disadvantage of conventional time-of-flight mass spectrometry is the expense of equipment used for pulsing of the ion source and the need to know the time of ion creation.